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Peroxisome proliferator activated receptor-γ ligands induced cell growth inhibition and its influence on matrix metalloproteinase activity in human myeloid leukemia cells

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Abstract

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is one of the best characterized nuclear hormone receptors (NHRs) in the superfamily of ligand-activated transcriptional factors. PPAR-γ ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. The present study was undertaken to investigate PPAR-γ ligands induced cell growth inhibition and its influence on matrix metalloproteinase MMP-9 and MMP-2 activities on leukemia K562 and HL-60 cells in vitro. The results revealed that PPAR-γ expression was detectable in the two kinds of leukemia cells; Both 15-deoxy-delta(12,14)-prostaglandin J2(15d-PGJ2) and troglitazone (TGZ) have significant growth inhibition effects on these two kinds of leukemia cells. These two PPAR-γ ligands could inhibit the leukemic cell adhesion to the extracellular matrix (ECM) proteins and the invasion through matrigel matrix. The expressions of MMP-9 and MMP-2 as well as their gelatinolytic activities in both HL-60 and K562 cells were inhibited by 15d-PGJ2 and TGZ significantly. We therefore conclude that PPAR-γ ligands 15d-PGJ2 and TGZ have significant growth inhibition effects on myeloid leukemia cells in vitro, and that PPAR-γ ligands can inhibit K562 and HL-60 cell adhesion to and invasion through ECM as well as downregulate MMP-9 and MMP-2 expressions. The data suggest that PPAR-γ ligands may serve as potential anti-leukemia reagents.

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Abbreviations

MMP:

Matrix metalloproteinase

PPAR-γ:

Peroxisome proliferator activated receptor-γ

15d-PGJ2:

15-deoxy-delta(12,14)-prostaglandin J2

TGZ:

Troglitazone

ECM:

Extracellular matrix

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Acknowledgements

We thank professor Jiang WQ for presenting microculture tetrazolium. We also thank the members of our laboratories for their insight and technical support. This work is supported by the grants from National Natural Science Foundation of China (No. 30471933).

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Authors and Affiliations

  1. Department of Haematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Guangzhou, 510630, P.R. China

    Jiajun Liu, Renwei Huang, Dongjun Lin, Xiangyuan Wu & Qu Lin

  2. Lab of Forensic and Biological Science, Medical College of Sun Yat-sen University, Guangdong Guangzhou, 510080, P.R. China

    Huiling Lu, Xinyao Wu & Jing Zheng

  3. Department of Hematology and Oncology, Qilu Hospital of Shandong University, Shandong Jinan, 250012, P.R. China

    Xianglin Pan, Jun Peng, Maohong Zhang, Ming Hou & Feng Chen

  4. Department of Oncology, Health Science Center of Peiking University, Beijing, 100083, P.R. China

    Yuqin Song

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  1. Jiajun Liu
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Correspondence to Jiajun Liu or Huiling Lu.

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Liu, J., Lu, H., Huang, R. et al. Peroxisome proliferator activated receptor-γ ligands induced cell growth inhibition and its influence on matrix metalloproteinase activity in human myeloid leukemia cells. Cancer Chemother Pharmacol 56, 400–408 (2005). https://doi.org/10.1007/s00280-005-1029-9

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  • DOI: https://doi.org/10.1007/s00280-005-1029-9

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